Department of Molecular Medicine and Medical Biotechnology, University of Naples 'Federico II', 80131 Napoli, Italy.
CEINGE-Biotecnologie Avanzate Scarl, 80145 Naples, Italy.
Int J Mol Sci. 2020 Jan 16;21(2):582. doi: 10.3390/ijms21020582.
The characterization of urinary metabolome, which provides a fingerprint for each individual, is an important step to reach personalized medicine. It is influenced by exogenous and endogenous factors; among them, we investigated sex influences on 72 organic acids measured through GC-MS analysis in the urine of 291 children (152 males; 139 females) aging 1-36 months and stratified in four groups of age. Among the 72 urinary metabolites, in all age groups, 4-hydroxy-butirate and homogentisate are found only in males, whereas 3-hydroxy-dodecanoate, methylcitrate, and phenylacetate are found only in females. Sex differences are still present after age stratification being more numerous during the first 6 months of life. The most relevant sex differences involve the mitochondria homeostasis. In females, citrate cycle, glyoxylate and dicarboxylate metabolism, alanine, aspartate, glutamate, and butanoate metabolism had the highest impact. In males, urinary organic acids were involved in phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, butanoate metabolism, and glyoxylate and dicarboxylate metabolism. In addition, age specifically affected metabolic pathways, the phenylalanine metabolism pathway being affected by age only in males. Relevantly, the age-influenced ranking of metabolic pathways varied in the two sexes. In conclusion, sex deeply influences both quantitatively and qualitatively urinary organic acids levels, the effect of sex being age dependent. Importantly, the sex effects depend on the single organic acid; thus, in some cases the urinary organic acid reference values should be stratified according the sex and age.
尿代谢组学特征分析可为每个人提供特征指纹，是实现个体化医疗的重要步骤。它受外源性和内源性因素的影响；其中，我们研究了性别对 291 名 1-36 月龄儿童尿液中通过 GC-MS 分析测量的 72 种有机酸的影响，并按年龄分为四组。在 72 种尿代谢物中，在所有年龄组中，4-羟基丁酸和高丝氨酸都是男性特有的，而 3-羟基十二烷酸、甲基柠檬酸和苯乙酸则是女性特有的。即使在年龄分层后，性别差异仍然存在，并且在生命的头 6 个月中更为明显。最相关的性别差异涉及线粒体稳态。在女性中，柠檬酸循环、乙醛酸和二羧酸代谢、丙氨酸、天冬氨酸、谷氨酸和丁酸盐代谢的影响最大。在男性中，尿液有机酸参与苯丙氨酸代谢、柠檬酸循环、丙氨酸、天冬氨酸和谷氨酸代谢、丁酸盐代谢以及乙醛酸和二羧酸代谢。此外，年龄特异性地影响代谢途径，只有男性的苯丙氨酸代谢途径受年龄影响。重要的是，两种性别中受年龄影响的代谢途径的排名不同。总之，性别深刻地影响尿有机酸的水平，无论是在数量上还是在质量上，而且这种影响与年龄有关。重要的是，性别影响取决于单一的有机酸；因此，在某些情况下，尿有机酸的参考值应根据性别和年龄进行分层。
